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Background and aims Limited data are available on the effectiveness and tolerability of direct-acting antivirals (DAAs) therapies in the real world for HCV-infected patients with comorbidities. This study aimed to describe the effectiveness of OBV/PTV/r +/- DSV (3D/2D regimen) with or without ribavirin (RBV) in HCV or HCV/HIV co-infected patients with GT1/GT4 and CKD (IIIb-V stages), including those under hemodialysis and peritoneal dialysis in routine clinical practice in Spain in 2015. Material and methods Non-interventional, retrospective, multicenter data collection study in 31 Spanish sites. Socio-demographic, clinical variables, study treatment characteristics, effectiveness and tolerability data were collected from medical records. Results Data from 135 patients with a mean age (SD) of 58.3 (11.4) years were analyzed: 92.6% GT1 (81.6% GT1b and 17.6% GT1a) and 7.4% GT4, 14 (10.4%) HIV/HCV co-infected, 19.0% with fibrosis F3 and 28.1% F4 by FibroScan (R), 52.6% were previously treated with pegIFN and RBV. 11.1%, 14.8% and 74.1% of patients had CKD stage IIIb, IV and V respectively. 68.9% of patients were on hemodialysis; 8.9% on peritoneal dialysis and 38.5% had history of renal transplant. A total of 125 (96.2%) of 135 patients were treated with 3D, 10 (7.4%) with 2D and 30.4% received RBV. The overall intention-to-treat (ITT) sustained virologic response at week 12 (SVR12) was 92.6% (125/135) and the overall modified-ITT (mITT) SVR12 was 99.2% (125/126). The SVR12 rates (ITT) per sub-groups were: HCV mono-infected (91.7%), HCV/HIV co-infected (100%), GT1 (92.0%), GT4 (100%), CKD stage IIIb (86.7%), stage IV (95%) and stage V (93%). Among the 10 non-SVR there was only 1 virologic failure (0.7%); 4 patients had missing data due lost to follow up (3.0%) and 5 patients discontinued 3D/2D regimen (3.7%): 4 due to severe adverse events (including 3 deaths) and 1 patient ' s decision. Conclusions These results have shown that 3D/2D regimens are effective and tolerable in patients with advanced CKD including those in dialysis with GT 1 or 4 chronic HCV mono-infection and HIV/HCV coinfection in a real-life cohort. The overall SVR12 rates were 92.6% (ITT) and 99.2% (mITT) without clinically relevant changes in eGFR until 12 weeks post-treatment. These results are consistent with those reported in clinical trials., MCL has served as consultant for AbbVie, MSD, Janssen, BMS and Gilead; MRB has received grant research from Gilead Science, and speaker fees from AbbVie, Gilead and MSD; MR has received speaker fees from AbbVie; MD has received grant support and consultancy fees from AbbVie, Bayer, Bristol-Myers Squibb, Gilead and Merck, Sharp & Dhome; FGR has served as speaker for AbbVie, Gilead and BMS; MLM has served as a speaker for AbbVie, BMS, Gilead, Janssen, MSD and ViiV; as a consultant for AbbVie, BMS and Janssen and has received research funding from FIPSE 36465/03, FIPSE 36680/07.-NEAT IG5 (NEAT is a project funded by the European Union under the 6th Framework programme) contract number LSHP-CT-2006-037570; MAC has served as a consultant for Gilead and and ViiV healthcare, and has received speaker fees from Janssens, Gilead, ViiV Healthcare; MMA reports personal fees from ViiV Healthcare, Gilead Sciences, Merck, Janssen, AbbVie and ABBOTT Laboratories, outside the submitted work; AR has received consultancy and speaker fees from AbbVie, Gilead Sciences and Merck Sharp & Dohme; JM has received honoraria, speaker fees, consultant fees or funds for research from AbbVie, BMS, Boehringer-Ingelheim, Gilead, Janssen, MSD, Roche and ViiV; EGP has received speaker fees from AbbVie and Gilead; LGB has served as consultant for AbbVie and Intercept and has received speaker fees from Gilead and MSD; AA, RMG, CB, TAE, MLG, BPL, IC, SB, LB, JGS, MJP, IMG, LM, IdlS, ML and JEL don't have a financial interest or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this paper; CdA and AM are paid employees of AbbVie and may hold stock or options. The specific roles of these authors are articulated in the 'author contributions' section. The design, study conduct, and financial support for the study were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the manuscript.

Resumen Introduccion GIDEON es un estudio internacional prospectivo, no intervencionista, que evaluo la seguridad de sorafenib en pacientes con carcinoma hepatocelular (CHC) no resecable en la practica clinica diaria, incluidos pacientes Child-Pugh B. Objetivos Analisis de datos recogidos en Espana sobre seguridad y efectividad de sorafenib y los patrones de tratamiento. Metodos Se recogieron los datos demograficos y de la enfermedad, la dosis inicial usada, los acontecimientos adversos emergentes del tratamiento (AA) y las modificaciones de dosis a lo largo del seguimiento. Se valoraron la supervivencia global y el tiempo hasta la progresion de la enfermedad. La eficacia y la seguridad se analizaron en funcion de la clasificacion Child-Pugh y la dosis inicial. Resultados Se incluyo a 143 pacientes de 19 hospitales espanoles. El 24,5% eran pacientes Child-Pugh B. El 90,9% de los pacientes recibio una dosis inicial de 400 mg/12 h. En pacientes Child-Pugh A se modifico mas frecuentemente la dosis y la duracion del tratamiento fue mas larga. La incidencia de AA y de aquellos relacionados con el farmaco fue similar en los pacientes Child-Pugh A y B, aunque los AA graves fueron mas frecuentes en los pacientes Child-Pugh B. Los mas frecuentes fueron diarrea, fatiga y eritrodisestesia palmo-plantar. La mediana de supervivencia global fue de 384 dias, y superior en pacientes Child-Pugh A (593 vs. 211 dias en Child-Pugh B); la mediana hasta la progresion de la enfermedad fue de 177 dias, similar en ambos subgrupos. Conclusion El perfil de seguridad de sorafenib en pacientes espanoles con CHC no resecable es independiente de la funcion hepatica. El estado Child-Pugh no parece influir en el enfoque de dosificacion de sorafenib ni en el tiempo hasta la progresion, pero si parece ser un fuerte predictor de la supervivencia.

GIDEON is a non-interventional, prospective, international study that evaluated the safety of sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in daily clinical practice, including Child-Pugh B patients.To analyze data collected in Spain on the safety and efficacy of sorafenib and treatment patterns.Data were collected during follow-up on demographic and disease characteristics, the initial dose used, treatment-emergent adverse events (AEs) and dose modifications. Overall survival was evaluated, as well as time to disease progression. Efficacy and safety were analyzed according to the Child-Pugh classification and the initial dose.We included 143 patients from 19 Spanish hospitals. A total of 24.5% of the patients were Child-Pugh B. An initial dose of 400 mg/12 h was used in 90.9% of patients. In Child-Pugh A patients, dose modifications occurred more frequently and the treatment duration was longer. The incidence of AEs and drug-related AEs were similar in Child-Pugh A and B patients, although serious AEs were more frequent in Child-Pugh B patients. The most common AEs were diarrhea, fatigue and hand-foot skin reactions. The median overall survival was 384 days and was higher in Child-Pugh A patients (593 vs. 211 days in Child-Pugh B). The median time to disease progression was 177 days, similar in both subgroups.The safety profile of sorafenib in Spanish patients with unresectable HCC is independent of liver function. Child-Pugh status does not seem to influence the approach to sorafenib dosage or time to progression but does seem to be a strong prognostic factor for survival.

Evaluation of submucosal lesions of the digestive tract with conventional endoscopy is unsatisfactory since this technique does not allow direct observation or correct evaluation of the size and layer of origin of the tumor; therefore, in most patients an etiological diagnosis cannot be established with this procedure. However, in most patients, endoscopic ultrasonography can resolve these problems: to a fair degree of certainty, this technique can differentiate malignant from benign lesions, measure their size, and establish their layer of origin. Endoscopic ultrasonography is the technique of choice to establish the presence and characteristics of submucosal tumors and their suitability for treatment. Moreover, this procedure can identify tumors that can be removed endoscopically without excessive risk. Hydrogastric ultrasonography can be an effective substitute for echoendoscopy when evaluating submucosal lesions and for staging tumors of the gastric antrum when echoendoscopy is not available or in patients in whom it cannot be performed. Hydrogastric ultrasonography is safe, inexpensive and very well tolerated by patients. We present the case of a female patient with a gastric GIST that was evaluated using hydrogastric ultrasonography. The size, layer of origin, and malignancy of the tumor were accurately established.

Endoscopy with biopsy sampling is the gold standard used in gastric cancer diagnosis. However, the positive predictive value of signs and symptoms for the diagnosis of carcinomas is quite limited, and, therefore, many patients are subjected to non-diagnostic endoscopies, especially when symptoms are not so specific. This study shows that ultrasonography is sensitive enough for the diagnosis of gastric cancer, and, therefore, use of this technique would further ensure a better selection of patients for endoscopy. The study included 143 patients (86 men and 57 women, with an average age of 68.6 years) who were suspected of having gastric cancer. The diagnostic accuracy of ultrasonography was evaluated in a blind study. The conventional technique was used in all cases. Demographic parameters and a series of other clinical-analytical variables were studied to look for possible gastric cancer predictive factors, which when present would make ultrasonographic results irrelevant. Statistical analysis was done using SPSS 12.0, wherein a value of P < 0.05 was considered to be statistically significant. Of the 143 patients studied, 40 were diagnosed to have gastric cancer. Sonography was able to diagnose 37 cases correctly, while there were three false negative findings and eight false positive findings. This results in 92.5% sensitivity, 92.2% specificity, 82.2% positive predictive value, 96.9% negative predictive value, and a global accuracy of 92.3%. Univariate analysis showed that persistent vomiting (P = 0.021), hemoglobin level of less than 8 g/dl (P = 0.045) and a positive ultrasonography result (P < 0.0001) were associated with a higher frequency of gastric cancer. Multivariate analysis showed that persistent vomiting, with an odds ratio for gastric cancer of 3.68 (95% confidence interval 1.15-11.79; P = 0.039), and a positive ultrasonography result, with an odds ratio for gastric cancer of 117.78 (95% confidence interval 32.45-427.49; P < 0.0001), could be considered as independent predictive factors for gastric cancer. It was concluded that ultrasonography is a very sensitive and specific technique for diagnosing gastric cancer. Gastric cancer was found to be present in just 28% of the patients studied, and their condition was suspect because of the clinical manifestations. Only vomiting and a positive ultrasonography result can be considered as independent predictive factors of gastric cancer.

Evaluation of submucosal lesions of the digestive tract with conventional endoscopy is unsatisfactory since this technique does not allow direct observation or correct evaluation of the size and layer of origin of the tumor; therefore, in most patients an etiological diagnosis cannot be established with this procedure. However, in most patients, endoscopic ultrasonography can resolve these problems: to a fair degree of certainty, this technique can differentiate malignant from benign lesions, measure their size, and establish their layer of origin. Endoscopic ultrasonography is the technique of choice to establish the presence and characteristics of submucosal tumors and their suitability for treatment. Moreover, this procedure can identify tumors that can be removed endoscopically without excessive risk. Hydrogastric ultrasonography can be an effective substitute for echoendoscopy when evaluating submucosal lesions and for staging tumors of the gastric antrum when echoendoscopy is not available or in patients in whom it cannot be performed. Hydrogastric ultrasonography is safe, inexpensive and very well tolerated by patients. We present the case of a female patient with a gastric GIST that was evaluated using hydrogastric ultrasonography. The size, layer of origin, and malignancy of the tumor were accurately established.